As the stomach turns…Pediatric GI Gems

1. As the stomach turns…Pediatric GI Gems Barb Bancroft, RN, MSN, PNP

2. Group A beta hemolytic strep • “I have a sore throat and I can’t swallow…” • “…and, my tummy hurts…” • Dehydration with drooling in young kids • How do you look at a toddler’s throat? • Digression: saliva

3. Enlarged tonsils • EBV infection of tonsils • Waldeyer’s ring (tonsils and adenoids) • Kids and sleep apnea; kids, lack of sleep and growth hormone • ?hypertension in kids? • Behavior disorders? ADHD? In kids? • Non-Hodgkin’s lymphoma

4. Oral signs of an eating disorder • The frequent vomiting and nutritional deficiencies often associated with eating disorders can severely affect health • 89% of bulimic patients have signs of tooth erosion; over time, loss of tooth enamel can be considerable • Hypertrophy of the parotid gland in women with eating disorders (serum amylase will be elevated) • Dry and cracked lips • Chronic dry mouth

5. The immunocompromised patient • Candida albicans (inhaled steroids in asthmatics) • Diabetics with hyperglycemia • Fungal infections and TNF-α antagonists (infliximab/Remicade; adalimumab/Humira; certolizumab/Cemzia etanercept/Enbrel) • HSV-1, HSV-2

6. Salivary glands—parotid, sublingual, submandibular • Parotid gland—MUMPS (kids and vaccines) • Acetylcholine innervates the salivary glands to produce saliva

7. OPEN Wide • Aphthous ulcers and celiac disease • Mouth clues to vitamin deficiencies • Vitamin C—gingivitis, dental erosion • Vitamin B2 (riboflavin)—stomatitis, cheilosis, geographic tongue • Vitamin B3 (niacin), B6 (pyridoxine), B12 (cobalamin), folic acid (B9)—glossitis

8. Say “ah”… • Soft palate and the uvula • Relationship of the pharyngeal musculature with CN IX (Glossopharyngeal) and X (Vagus) • Swallowing • What is the hardest thing to swallow?

9. Causes of nasal speech • Cleft palate (folic acid!!) • Glossopharyngeal nerve palsy—(viral) • Guillain-Barré syndrome with bulbar onset (cranial nerve onset vs. ascending paralysis beginning with the longest nerves first—ie. the feet) • #1 cause of Guillain-Barré?

10. Let’s go back to the tonsils, shall we? • Waldeyer’s ring—adenoids and tonsils • Lymphatic tissue • Growth hormone is produced at night • Adenoiditis/tonsilitis • Enlarged? Sleep apnea? Behavior disorders? ADHD?

11. Is it GER or is it GERD? • GER—Gastroesophageal reflux (regurgitation and vomiting are a normal part of infant life—physiologic reflux) • Passage of gastric contents into the esophagus—peak at 4-6 months (41%); decline after the first birthday with less than 5% aged 13-14 months) • 1.8% to 22% in children aged 3 to 18

12. What is GERD? • ACID is the bad guy • Physiologic sphincter (LES)—DA/ACH • With GERD--decreased pressure in the lower esophageal sphincter due to drugs*, nicotine, alcohol, fatty foods, obesity, increased pressure in stomach (late evening meal) • So, how about a pizza, cold beer and a cigarette before bedtime? • *What drugs? Beta agonists (bronchodilators in kids with asthma)

13. Digression • Biological rhythms—normal input to LES at night and to bronchioles • GERD and acid reflux—stimulates vagus nerve to release acetylcholine to tighten LES • Vagus also tightens bronchioles—cough, dyspnea, wheezing in patients with OPD (ROAD, COPD) • RX?

14. What are non-drug ways to reduce GERD? • Dietary changes? For infants with GERD—smaller, more frequent feeds; thickened feeds with rice cereal or carob bean gum thickener • Don’t overfeed • Consider intolerance to cow’s milk for “GERD-like” symptoms • Upright feeding position; supine to sleep; small pillow or a folded blanket where infant sits in car seat to extend hips and decrease intraabdominal pressure

15. Pharmacology of GERD for kids • H2 RA (receptor antagonists)—over-the-counter • Tagamet (cimetidine)(≥16 yo), Zantac (ranitidine) (1 month to 16), Pepcid (famotidine)(1 year to 16), Axid (nizatidine)(≥12)(take at bedtime) • PPIs (Proton Pump Inhibitors) are more potent acid suppressors than H2RA—the “prazoles”; take 30 minutes before breakfast • Omeprazole (Prilosec)(2-16), lansoprazole (Prevacid)(1-17), and “the purple pill”—esomeprazole (Nexium)(12-17)**

16. Has your patient been on the “prazoles” for longer than 5 years? • The parietal cell that pumps acid also pumps out intrinsic factor (IF) • Intrinsic Factor is necessary for the absorption of B12 from food • If you stop pumping the acid into the stomach, you also stop pumping intrinsic factor for B12 absorption • May also be caused by an autoimmune disease with antibodies against IF (pernicious anemia); kids with type 1 diabetes may also have pernicious anemia • No acid, no calcium (kids and bones) • No acid, no iron (check for iron deficiency anemia)

17. Selected conditions • Gastroenteritis—peri-umbilical pain • Acute diarrhea—watery—think viral? Bloody—think more invasive, bacterial? • Acute appendicitis—no more than a 5-day disease; periumbilical pain followed by pain in the RLQ; increased WBC with left shift; fever; psoas sign; “the walk”

18. Selected conditions • Child abuse injuries • The second most common cause of death from child abuse is injury to abdominal organs • Small intestine, especially the duodenum, followed by mesenteric hemorrhage and liver lacerations • Accidental abdominal injury—spleen, kidney

19. Child abuse and bruises • “The skin and the bones tell a story that the child is either too young or too frightened to tell.” • Normal bruises are facial scratches, one bruise on forehead (toddler), knee and chins • French proverb: “The mother of a child who elects to re-wed, has taken the enemy into her bed.” • A child living with a stepparent is 100 times as likely to suffer fatal abuse.

20. Age of bruise • Is it red, purple, blue? • Green, yellow, brown? • Reddish/blue less than 1 day, immediate • Blue/purple 1-5 days • Green 5-7 days • Yellow 7-10 days • Brown 10-14 days • Resolution 2-4 weeks

21. Normal bruises in kids… • Facial scratches in babies from long fingernails • Knee and shin bruises due to usual wear and tear of playing rough and tumble • Single bruise on the forehead of a toddler • Bruises on bony prominences such as the knees and elbows

22. The stomach • “Whoever said the way to a man’s heart is through his stomach flunked geography…” --anonymous • The stomach is a saccular organ with a volume of 1200 to 1500 ml but a capacity of greater than 3000 ml

23. Gastric acid • At maximal secretory rates, the stomach intraluminal concentration of hydrogen ion is 3 million times greater than that of the blood and tissues • The mucosal barrier protects the gastric mucosa from autodigestion and is created by: • mucus secretion; • bicarbonate secretion • epithelial barrier and, • mucosal blood flow • Truly a physiological marvel, or gastric walls would suffer the same fate as a T-bone

24. Peptic ulcer disease • Usually solitary lesions less than 4 cm in diameter • Duodenum, first portion • Stomach, antrum • GE junction, in the setting of GERD • 4 million people have peptic ulcers; 350,000 new cases per year, 100,000 hospitalized, 3000 die • Male/female for duodenal = 3:1; male/female for gastric = 1.5 to 2:1 • Imbalance between the gastroduodenal mucosal defense mechanisms and the damaging forces—gastric acid and pepsin • Hyperacidity is NOT a prerequisite • H. pylori is present in 100% of duodenal ulcers and about 70% of patients with gastric ulcers

25. Gastric ulcers (peptic ulcer disease) • Helicobacter pylori—the most common infection worldwide • Elaborates urease and produces ammonia which buffers gastric acid in the immediate vicinity • Gastric ulcers • Chronic inflammation (gastritis) and regeneration of the antrum • The only bacteria known to be “oncogenic” • Is it normal flora? • How do you “catch” it? • How do you treat it? • Is H. pylori a good thing?

26. Gastric ulcer caused by NSAIDS • 2.74 RR of any GI complication • If over 50, RR is 5.57 • RR 12.7 with NSAIDS and warfarin; 4.76 with NSAIDS and steroids • PPIs decrease ulcer/ bleed by 4-fold

27. The duodenum (12 fingerbreadths), —the organ of nausea • 5-HT3 (serotonin) receptors) • Serotonin release causes nausea--Makes ya’ sick to your duodenum • 5-HT3 blockers--The “setrons”—ondansetron (Zofran), granisetron (Kytril), doasetron (Anzemet), palonosetron • Adding ondansetron to oral rehydration in kids reduces nausea and vomiting and decreases the need for IV fluids by greater than 50% • Bariatric surgery, Type 2 DM, and kids

28. Celiac disease and the duodenum • 1 in 250 in U.S.; greater prevalence in 1st and 2nd degree relatives; ?duration of breast feeding; age at which a person ingests gluten; cigarette smoking • Autoimmune disease—HLA-DQ2; HLA-DQ8 • Ingested gluten crosslinks with tissue transglutaminase released in the lamina propria and epithelium of the small intestine • Immune system helper T cells (CD4 cells) release cytokines IF-γ and IL-4 which damage villi; flattened villi and malabsorption • Anti-transglutaminase antibodies

29. Celiac disease • Absorption problems result in anemias—iron deficiency (growth problems in kids); folate deficiency; calcium absorption problems (osteopenia) • Always check for osteopenia and osteoporosis in your long-term patients with celiac disease! • aphthous ulcers are strongly associated w/ celiac disease (This Week in Medicine, MDConsult, 1/31/07)

30. Celiac disease • Classic symptomatic presentation characterized by diarrhea, abdominal pain, weight loss, flatulence, and nutritional deficiencies • Atypical presentation characterized by gait ataxia, seizures, peripheral neuropathy, aphthous stomatitis, arthritis, migraine headaches • Associated with other autoimmune diseases—Type 1 diabetes, autoimmune myocarditis, primary biliary cirrhosis • Gluten-free diets and the improvement of symptoms

31. Gastroenteritis… • Umbilicus (belly button)—embryologic origins with colon (Homer and Dr. Colón) Word o’ the day… Omphaloskepsis (om-fuh-lo-SKEP-sis); noun • Definition: Contemplation of one’s navel. (From Geek omphalos (navel) + skepsis (act of looking, examination) • Peri-umbilical pain • Causes of gastroenteritis—food poisoning, viral infections, bacterial infections

32. Gastroenteritis • Infectious gastroenteritis—causes more than 12,000 deaths per day from dehydration among children in developing countries and constituting one half of all deaths worldwide before age 5 • Attack rates of one to two illnesses per person per year in U.S.—results in an estimated 99 million acute cases of either vomiting or diarrhea per year—approximately 40% of the population

33. Viral gastroenteritis • Rotavirus—140 million cases and 1 million deaths worldwide per year; 6 to 24 months of age; shed 1,000,000,000,000 (10¹² particles)/ml of stool (the minimum infective inoculum is only 10 particles, hence the rampant outbreaks in daycare and pediatric populations in hospitals) • Norwalk virus (norovirus)—rare in young kids

34. Noroviruses • Responsible for majority of nonbacterial food-borne epidemic gastroenteritis in older children and adults; • Salad bars (cold foods, raw shellfish), person-to-person,water on cruise ships • Has also been found in the community and in nursing homes • Vicious cycle of vomiting and diarrhea for an average of 23 hours—known as “shuking” • start shedding virus before symptoms occur and shed virus for 4 days after symptoms subside (hence, the rapid spread of infection); can shed virus up to 4 to 8 weeks after illness

35. Bacterial entercolitis • Ingestion of preformed toxin in food—Staphylococcus aureus, Vibrio species, Clostridium perfringens • Infection by toxigenic organisms, which proliferate in the gut lumen and elaborate an enterotoxin (Cholera toxin is the prototype secretagogue) • Infection by enteroinvasive organisms, which proliferate, invade, and destroy mucosal epithelial cells (Salmonella, Yersinia enterocolitica)

36. Acute appendicitis • Acute appendicitis presents initially with peri-umbilical pain and subsequently localizes to the right lower quadrant (RLQ) • High risk occupation for acute appendicitis? • Pig farmers

37. Food-borne illness and gastroenteritis

38. Salmonella in raw or undercooked eggs and chicken • Pasteurized eggs for “seizure” salad (Caesar salad), eggnog, and guacamole • Salmonella in chicken • No more sunny-side up, especially for high-risk patients (unless the eggs are pasteurized)

39. Digression: • Salmonella in reptiles—snakes, turtles, iguanas

40. Campylobacter jejuni • Undercooked chicken • Cuddly puppies • 180º whole chicken • 170º white meat • 180º dark meat

41. E. Coli 0157:H7—the “burger” bug • 3rd most deadly toxin in the world • 10-100 pathogens to make you ill or kill you • Very young, very old, very immunocompromised • Acute Renal Failure in Kids—hemolytic uremic syndrome • Swimming pools, petting zoos • Mickey D’s—30 outbreaks per year • Supportive Treatment • Prevent—cook burgers to 160º F

42. Spinach • Produce is the biggest offender for E.Coli O157:H7 • Parasites and salmon sushi; raw fish

43. Crohn’s disease—inflammatory bowel disease • Primarily small bowel, but can include anywhere from the esophagus to the rectum • Skip lesions; fistulas; strictures • Cause? Bacteria? Mycobacterium paratuberculosis? • Autoimmune response

44. Signs and symptoms • Usually begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain, spaced by asymptomatic periods lasting for weeks to many months • 1/5th of patients with abrupt onset, with acute RLQ pain, fever, and diarrhea • Diff dx suggesting acute appendicitis or acute bowel perforation • Chronic disease with fibrosing strictures, marked loss of albumin, generalized malabsorption, B12 malabsorption, or malabsorption of bile salts leading to steatorrhea

45. Treatment • Methotrexate to reduce the immune response • Inflammation via TNF-alpha • Drugs that block TNF-alpha include infliximab (Remicade), adalimumab (Humira), etanercept (Enbrel) • Certolizumab pegol (Cemzia)

46. Ulcerative colitis—inflammatory bowel disease • Limited to the colon and affects only the mucosa and submucosa; extends in a continuous fashion proximally from the rectum • Peak onset between 20 and 25 years of age • Risk for colon cancer—risk is highest in patients with pancolitis of 10 or more years duration; 30% @ 35 years after dx • Dysplasia (distortion of the normal orientation and architecture of cells)—low-grade dysplasia vs. high-grade dysplasia and ulcerative colitis

47. Antibiotic-associated diarrhea • “the usual, run-of-the-mill diarrhea” vs. • Clostridium difficile diarrhea (new strain)—the “floxacins” and Clindamycin are the biggest offenders for C. difficile

48. Clostridium difficile • Clostridium difficile (difficult to culture, hence, difficile) and soap and water kill spores better than alcohol-based gels • New strain (2003) produces more toxin and causes more severe outbreaks—produces 16x more toxin A and 23 times more toxin B; characterized by the deletion of a gene that downregulates the production of both toxins • Major risk factor? Use of the fluoroquinolones; Other antibiotics? Amox/Ampicillin, 2nd/3rd generation cephalosporins

49. A few more notes on C. diff • Has the child had dental work with prescribed antibiotics? • Treatment—vancomycin, metronidazole • Stool transplants in chronic C. diff • High risk of recurrence in patients over 65, patients with severe underlying disease, and additional antibiotic use after discontinuing therapy for C. diff. • Surawicz CM. Reining in recurrent Clostridium difficile infection—Who’s at risk? Gastroenterology 2009 Apr;136:1152.

50. The sheep • You wanna do WHAT with my intestines? • Clinical uses of a sheep’s cecum